Total synthesis of (-)-2-hydroxy-N-methylmorphinan-6-one and its (+)-enantiomer has been achieved. Deoxygenation of these isomers afforded the optically active, aromatic unsubstituted 6-ketomorphinans. A chemical conversion of a (-)-4-hydroxy-substituted 6-ketomorphinan, prepared from nat. morphine, into its (-)-1-hydroxy isomer and its O-methyl ether has been accomplished. The 1- and 2-oxygenated ketomorphinans showed remarkably little antinociception, whereas the aromatic unsubstituted (-)-isomer was highly active. It is now established that the oxygen substitution in 6-ketomorphinan is best at C-3, C-4 and C-3,4. The O-methyl ethers of these phenolic ketomorphinans are more potent than the parent phenols in the 6-ketomorphinan series, and less potent in the morphinan series. N-Phenethylation and N-allylation or N-cycloalkylation increased potency or antagonism response.